Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: Monogenic Diabetes (MFD) represents close to 2% of all the cases of diabetes diagnosed in people younger than 45 years old. Maturity-Onset Diabetes of the Young (MODY), neonatal diabetes, and several syndromic forms of diabetes are included among the most accounts for about typical forms of MDF. MODY is the most frequent type of MFD, with MODY 1, 2, 3, and 5 being the most prevalent forms. The aim of this narrative review is to describe pregnancy associated changes in the pharmacological profile of the antidiabetic drugs used in women with the most frequent MODY subtypes.

Methods: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/ PubMed, EMBASE, and SCIELO databases from 1970 to 2019 first semester.

Results: Pregnancy introduces changes in the pharmacodynamic and pharmacokinetic profile of some of the treatments used in MODY. MODY 3 (also known as HNF1-A MODY) is the most frequent MDF. MODY 3 patients are highly sensitive to Sulfonylureas (SU). This is also the case for MODY pregnant women. This high sensitivity to SU is also registered in patients with MODY 1 (HNF4-A MODY). Pharmacodynamic changes have been proposed to explain this behavior (Epac2 hyperactivity). However, changes in expression/activity of the metabolizing CYP2C9 cytochrome and/or alterations in the drug transporters oatp1 (Slc21a1), Lst-1 (Slc21a6), OATPD (SLC21A11), and oat2 may better explain, at least in part, this phenomenon by an increase in the concentration of the active drug.

Conclusion: The impact of changes in the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in a pregnancy complicated by MODY is unknown. However, switching-to-insulin recommendation formulated for MODY 1 and 3 seems to be justified. Further research in this field is needed for a better understanding of changes in drug activity associated with this particular subset of patients with MFD.

Background: Hesperetin has antihyperuricemia activity, and the pharmacokinetic profiles of hesperetin may be altered by hyperuricemia. This study aimed to develop a highly sensitive and specific method for the determination of hesperetin in normal and hyperuricemia rats, and to compare pharmacokinetic profiles of hesperetin after oral administration between normal and hyperuricemia rats.

Methods: Sprague-Dawley (SD) rats were randomly divided into one normal group (group A) and four hyperuricemia groups (group B, C, D, and E). Groups A, B, C, and D received a single dose (9-81 mg/kg) of hesperetin on Day 28, respectively, while group E received multiple doses (27 mg/kg) of hesperetin once daily for 28 days. Blood samples were collected at 10 different time points post-dose, and hesperetin was determined by Ultra-high Performance Liquid Chromatography- tandem Mass Spectrometric (UPLC-MS/MS).

Results: Compared with normal condition of group A, hyperuricemia of group C induced 48.19% and 19.57% decreases in Cmax and CL/F, and resulted in 58.25% and 19.48% increases in Tmax and AUC0-t for hesperetin, respectively. After 28 days of hesperitin treatment, Cmax of group E was significantly elevated than that of group C (p < 0.05). Hesperetin exhibited nonlinear pharmacokinetic properties in the range of 9-81 mg/kg in hyperuricemia rats.

Conclusion: The pharmacokinetic parameters of hesperetin in hyperuricemia rats were reported for the first time. Intestinal injury may be ameliorated by hesperetin in hyperuricemia rats after 28 days' treatment. These findings could provide more beneficial information to the mechanism and clinical applications of hesperetin.

Inflammatory Bowel Diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the '50s, are still the mainstay of treatment for moderate to severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on the long-term natural history of the disease, the steroid-sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so-called "low bioavailability" steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and a more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines.

Background: Green tea has been extensively studied for its potential health benefits against diseases, such as cancers, cognitive degenerative diseases, and cardiovascular diseases.

Methods: The authors undertook a structured search of peer-reviewed research articles from three databases including PubMed, Embase, and Ovid MEDLINE. Recent and up-to-date studies relevant to the topic were included.

Results: Green tea extract exerts its functions by interacting with multiple signalling pathways in human cells. Protein tyrosine kinase is one of the examples. Abnormal activation of tyrosine kinase is observed in some tumour cells. Green tea extract inhibits phosphorylation, reduces expression, or attenuates downstream signalling of epidermal growth factor receptor, insulin-like growth factor receptor, vascular endothelial growth factor receptor, and non-receptor tyrosine kinase. Combination of green tea extract with tyrosine kinase inhibitors may provide synergistic effects by overcoming acquired resistance.

Conclusion: Green tea extract can affect multiple receptor targets. In the current review, we discuss the pharmacological mechanisms of green tea on tyrosine kinases and their implications on common diseases.

Background: Over the years, drug monitoring-such as Anti-Drug Antibodies (ADA) dosage- has witnessed major transformations. In fact, ADA are more and more used in rheumatology and gastro-enterology in monitoring chronic inflammatory disease therapeutic response. The main purpose of those researches is to produce less immunogenic drugs and, in consequences, to improve tolerance and efficiency since immunogenicity of those drugs still is the main constraint to their long-term use. The aim of this review was to highlight anti-drug-antibodies potential effects on the pharmacokinetics and bioavailability of biotherapies as well as their clinical implications.

Methods: For this purpose, we collected and summarized published data on PubMed using keywords "Biologics, Rheumatoid Arthritis, Spondyloarthritis, Crohn disease, Anti-drug antibodies, residual rate, immunogenicity, efficacy, tolerance". The time-period selected for this study was 2000-2019.

Results: Anti-Drug-antibodies decrease the pharmaco-availability of drugs and, in consequences, its efficiency and high risk of refractory diseases and side effects.

Conclusion: Recent literature is consistent with the fact that drug monitoring using ADA dosage coupled with residual drug concentration offers reliable options to comfort practitioner' therapeutic management decisions. This is particularly interesting in failure of treatment or in side effects onset situations.

Rationale & objective: Rodenticide poisoning, either accidental or intentional, is very common in rural India. The absence of a definite antidote made it a major concern with a high mortality rate. Therefore, this study aimed to assess the effectiveness of N-Acetyl Cysteine (NAC) in rodenticide poisoning as there are recent positive shreds of evidence on it.

Methodology: A retrospective study was conducted in a tertiary care teaching hospital on patients admitted with rodenticide poisoning during a period of 2012-2017. The Fischer's exact test and relative risk were measured to analyze the outcome of treatment and risk factors, respectively.

Results: A total of 229 patients were enrolled in the study with a mean age of 30.04 ± 15.67 years. The suicidal attack was the major (86.0%) reason for poison consumption. The survival rate was significantly (p ≤ 0.03) higher in the NAC treatment group compared to the non-NAC group. Moreover, the majority (93.4%) of participants did not experience any adverse effects. The mean oral loading dose and maintenance dose was 7580.95 ± 2204.29 mg and 3694.53 ± 2322.58 mg, respectively. Yellow Phosphorus poisoning (Relative Risk [RR] 2.888 (1.179-7.079); p=0.020) and Time lag of ≥ 24 hours (RR 3.479 (1.137-10.645); p=0.029) were the significant risk factors for mortality.

Conclusion: NAC is shown to have a significant survival benefit with a good safety profile among rodenticide poisoners. Further adequately powered prospective researches with more emphasis on dosing parameters are warranted for better quantification in different settings and for clinical implementation.

Background: Poisoning is one of the leading causes of childhood morbidity and mortality worldwide. Despite the advancement of poison detection by modern investigation methods, the clinical skill of toxidrome recognition by combining the findings from a detailed history, thorough physical examination, and the results of basic investigations is still indispensable for the management of children with suspected poisoning.

Objective: The aim was to review pediatric toxidromes and poisoning management.

Methods: A literature search was conducted on PubMed (between February 1 and 15, 2020) with keywords "toxidrome" "poisoning" "intoxication" "children" and "pediatric". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article.

Results: Toxidrome recognition may offer a quick guide to possible toxicology diagnosis so that specific antidote can be administered in a timely manner. This article discusses a few commonly encountered toxidromes in pediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are also discussed. Although most patients with intoxication can be managed with close observation, supportive measures and antidote treatment, it is unfortunate that antidotes are only available for a limited number of poisons responsible for intoxication. Extracorporeal toxin removal is being increasingly recognized as a mode of treatment for patients with rapid deterioration who are unresponsive to conventional management. The decision to apply such technique and the choice of modality are frequently individualized due to the paucity of high-level evidence. The various patient and toxin/medication factors involved in the decision- making process are discussed.

Conclusion: Poisoning is a common cause of pediatric accidents and injuries. Physicians should be familiar with common toxidromes and poisoning management.

Background: The prevalence of cholelithiasis in developed countries is high and its cause is multifactorial, with a negligible proportion of drug-induced cholelithiasis.

Methods: Relevant studies were identified by PubMed, Google Scholar and Science Direct. Reference lists of retrieved articles were also reviewed. The most relevant and up-to-date information was incorporated.

Results: There is a wide range of drugs that can induce lithiasis. While the risk of developing lithiasis is high with some drugs (ceftriaxone, atazanavir, somatostatin analogues), it is lower or even questionable with others. Some drugs precipitate in the bile and may account for up to 100% of the weight of the stone.

Conclusion: Cholelithiasis can be induced by a wide range of drugs with different mechanisms of action. The aim of the article is to draw attention to this lesser known fact and the need to take into account the risk of developing lithiasis prior to therapy initiation.

While facing potentially high morbidity from COVID-19 without known effective therapies, the off-label use of several non-specific drugs has been advocated, including re-purposed anti- viral (e.g., remdesivir or the lopinavir/ritonavir combination), biologic agents (e.g., tocilizumab), and antimalarial drugs such as chloroquine and hydroxychloroquine, in association with or without azithromycin. Data regarding the effectiveness of these drugs in treating COVID-19 has been shown in some trials and clinical settings, but further randomised controlled trials are still being carried out. One of the main concerns regarding their widespread use, however, is their possible effects on the QT interval and arrhythmogenic potential. Some of these drugs have been associated with QT prolongation and Torsades de Point, a potentially lethal ventricular arrhythmia. The review aims to highlight the magnitude of this problem, to quickly refresh clinically impacting cornerstones of QT interval and TdP pathophysiology, to summarize the available evidence regarding the QT and arrhythmia impact of drugs used in different clinical settings in COVID-19 patients, and to help the physicians dealing with the knowledge needed in the everyday clinical duties in case of doubts regarding QT-induced arrhythmias in this time of emergency.

Background: Signal strength for any drug-event combination can be determined using disproportionality analysis. Vemurafenib is a BRAF inhibitor approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of metastatic melanoma. This study aims to identify the signal strength of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with vemurafenib using disproportionality analysis in FDA database of Adverse Event Reporting System (FAERS).

Methods: Data were obtained from the public release of data in FAERS. The case/non-case method was adopted for the analysis of the association between vemurafenib use and DRESS. The data mining algorithm used for the analysis was the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). A value of ROR-1.96SE>1, PRR≥2 was considered as positive signal strength.

Results: A total of 7,171 reports for DRESS have been reported in the FDA database. Amongst which, 125 reports were associated with vemurafenib. A cumulative ROR of 17.72 (95% CI 14.83; 21.18) and PRR of 17.46 (95% CI 14.65; 20.81) were observed. Combination treatment of vemurafenib with cobimetinib had a higher number of reports (100) with ROR of 103.42 (84.13- 127.14) and PRR of 94.52 (78.26- 114.15). Four deaths were reported and the non-death serious reports included hospitalization, life-threatening, disability, and other serious events with 61, 11, 2 and 39 reports, respectively.

Conclusion: Positive signal strength was observed for vemurafenib associated DRESS. The signal strength was higher for vemurafenib in combination with cobimetinib than vemurafenib alone. Health care professionals should be cautious about encountering serious adverse events and should report such events to the regulatory authorities.